New organic sulphonamido isothiocyanates



Unit SW Patent NEW ORGANIC SULPHONAMIDO ISOTHIOCYANATES Herbert AubreyStevenson, John Ray Marshall, and Anthony Frederick Hams, Nottingham,England, assign- 'ors to Boots Pure Drug Company Limited, Notting- 1ham, England, a British company No'Drawing. Filed Jan. 29, 1953s. No.636,873 Claims priority, application Great Britain Feb. 3, 1956 11Claims. 01. 260-2393 This invention relates to new organicisothiocyanates which have been found to possess valuable properties.The invention consists in compounds of the general formula:

in which the phenyl nucleus X is substituted by at least oneisothioc'yanato radical, R is hydrogen or an alkyl radical, R is analkyl radical, an alkyl radical containing a phenyl substituent, acycloalkyl radical, an alke'nyl radical, a phenyl radical or a phenylradical containing one or more halogen atoms, alkyl, alkoxy or nitroradicals as substituents, or R and R together with the nitrogen atomrepresent a heterocyclic radical as hereinafter We have now found thatdusts, dispersions, emulsions, V

smokes and aerosols of the compounds of the above general Formula I haveproperties which render them valuable for the control 'of fungi forexample Ventur'id inaequalis, Botrytis cinerea, Sclerotinia fructigena,Til letia caries, Pythium debaryanum, Corticium sola'r'ii,

Podosphaera leucotricha and Cladosporiur'rt fulvum. Our inventionconsists therefore in the compounds of the oral formula together with adiluent or carrier.

The compounds of the invention may be prepared by.

methods which are well-known in the art for the syn phosgene on thecorresponding amines of the general formula:

above general Formula I and in compositions which con tain as activeingredient a compound of the above gena position with water.

2,980,668 Patented Apr. .18, .1961

in the above general formulae may be derived from a heterocycliccompound containing a secondary nitrogen atom, such as for example,piperazine, morpholine and partially or completely .reduced pyridine andpyrrole compounds.

The dispersions having a solid dispersed phase according to theinvention may comprise the active ingredient in combination with adispersing agent and/or a suspending agent in aqueous medium. Forconvenience the preparation may consist of active ingredient admixedwith a dispersing agent and/or a suspending agent such that a dispersionis formed when the mixture is added to water. To facilitate theformation ofa dispersion in this manner, the preparation to be dilutedmay also contain a water-miscibleorganic solvent, for example, acetone.

The dispersions according to the invention also include 'or an aromaticsolvent boiling within the range 80-300" C. It'may be advantageous toadd a non-volatile vegetable or inineral oil such as liquid paraflin toact as an activator and/or sticker. The emulsion composition accordingto the invention may also contain a wetting agent. For convenience thecomposition may consist of the active ingredient admixed with or insolution in 35 an organic solvent as hereinbefore specified togetherwith an emulsifying agent, and if desired, a Wetting agent such that anemulsion is formed on admixing the com- Such compositions also form-partof the present invention. The aqueous dispersions and emulsions hereindescribed may. be diluted with water before application to obtain afinal concentration of the active ingredient within the range 0.00l-10%w./v. but

the inv ention is not limited to compositions which contain thisconcentration of the active ingredient; the concentration of thesolutions which are employed depends upon the requirements of theparticular spraying machine thesis of organic isothiocyanates. Thus thecompounds L Whihis to be used.

of the invention may be prepared by the action of thio Dispersions ofthe active ingredient in whichthe carrier [is 1a;pulverulent soliddiluent also form part of the presw/v. of the active ingredient.

We have found that it is possible to employ the compound of theinvention in the form of smokes and 7 general Formula I.

In; the preparation of compositions suitable for dispersion asaerosols'which contain as active ingredient compounds of the abovegeneral Formula I, the active ingredient may be dissolved in a volatilesolvent such as acetone. Alternatively the active ingredient may bedissolved in a high boiling aromatic solvent such as xylene or anon-volatile oil such as vegetable oil together with a supplementarysolvent such as cyclohexanone or acetone if desired. Such compositionsare readily dispersed as aerosols either by mechanical means or byincorporating therein a volatile propellant such as Freon (a mixture ofchlorofiuoro derivatives of methane and ethane).

Compositions suitable for the generation of fungicidal smokes comprisethe active ingredient in association with an ignitable slow burningcomposition such that a smoke containing the active ingredient isgenerated on ignition.

The Wetting and emulsifying agents which are employed in thecompositions ofthe invention should preferably be free of amino groupsand alcoholic groups so as to avoid the possibility of condensationtaking place between the active ingredient and one of the aforementionedgroups with theformation of tln'oureas and thiourethanes respectively.'In the case of compositions which are to be subjected to prolongedstorage and which contain a compound of the invention dissolved inanorganic solvent the latter should preferably be substantially anhydrousasthe presence of water in such solutions tends to cause hydrolysis ofthe active ingredients on storage. I

Other insecticides and fungicides such as D.D.T. benzene hexachlorideand sulphur may be incorporated in the compositions of the inventionbefore application of the latter to the plants. V g V V The compounds ofthe invention have been demonstrated to possess funcigidal activity intests carried out in the following manner:

LABORATORY TESTS (1) Spore germination test.--The test is based on therecommendations of the American Phytopathological Committee (1943). On aglass slide a deposit of known weight of the compound under test isformed by allowing an acetone solution of known concentration of thecompound to evaporate. Spores of one of a number of pathogenic fungi inaqueous suspensions are set on these deposits to germinate and thepercentage germination is noted. In Table I the results of these testsare shown, the approximate L.D. 50 being the concentration in parts permillion of the acetone solution of the substance under test which iscalculated would inhibit. 50% of the spores from germinating; the higherthe value of the L.D. 50 the lower theactivity of the compound. Thefigures shown in the column headed Derived L.D. 50 are obtained bysuspending spores in a series of solutions of graded dilutions of thesubstance under test and assessing the concentration causing 50%inhibition of germination. The test solutions are prepared by dilutionwith water of a 5% w./v. solution of the substance in acetone. In TableI the symbols B.c., S.f., C.f., and V.i. represent the fungi Botrytiscinerea, Sclerotinia fructigena, Cladosporium fulvum and Venturiainaequalis respectively.

Table! R,\ /N-EO|NCS .34 w

.Approximate L.D.50 Derived- R1 Rs L.D.50

" I Vi.

3.1:. S]. OJ. VJ.

Methyl 12 p a s Cyclohexyl 2 2 3 Ethy 12 12 50 lsoPrnpyl 12 12 6 n-Buty1.5 1 1 n-Propy 1.5 2 1.5 Benzy .3 2 w 3 Phenyl 3 2 1.5 isoBntyl 16 1.51.5 p-Chlorobenzyl ,3 1.5 i 1.5 n-Penty 1 1 1 p-Tnlyl 3 1 1p-Methoxyphenyl-.. 3 1 1.5 o-Tolyl 8 1.5 1.5 ar rs--- 2 a a pnxyp enynflepty 400 400 2 n-Hexy 400 400 200 Allyl 8 1 1.5 3-Methylbutyl 3 1. 512 Sec'Butyl 6 '4- 1. 5 4-MPthylT ent vl. 4 1.5 g 1.5 m-Nltmphen vl..-8 1. 6 12 o-Methnxyphenyl 12 3 1.5 o-(hl rophenyl 6 V 1.5 n .12 Methyl 33 12 Ethyl..-- 3 1.5' 1.5 nButyL- 400 400 1 lsoRutyl 400 400 6 n-Prnpyl-6 6 1 Phenyl.-- 2 2 2 --do 200 400 2 do. 400 400 200 Benzyl- 400 6 1. 6PhenyL. 400 6 50 Plperldyl 8 6 2 Morph lyl 50 12 2 Pyrrfllldyl 6 1.5 23-Methylplperldyl. 6 400 400 2Mcthylpiperldyl..- 4 3 1. 54-Methylpiperidyl.-. 50 1. 5 2 A -Tetruhydroy yrldyl 1.5 2 1.5

-(2) B mf e t em- A m r Qi hQ-FQmPuQd-i of; the invention have beentested in the following mane,

net, Seeds of wheat are. infected with Tilletia caries and dressed withdusts containing 10% w./w. of the Sub! tseet plant s pr yed o u i t anan seas ns usp nsiew containing 0.05% wf/v. of the compound underttest.When the spray deposit is dry. the plants are enclosed in a, chamber inamoist atmosphere at a temperature Key: C-complete control. C+==95%control. P=50% or more control.

EXTENSION rests stance under test in kaolin at the rate of 2 ozs. ofdust 5, t 75 F. and the plants are inoculated with spores of; per bushelof seed. The dressed seeds are incubated Cladqsporium fulvum. A group ofuntreated plantsis for days on agar and at the endgof this timethe seedsinoculated in a similar manner. The plantsare kept un-. are removed fromthe agar and the spores of the fungus der these conditions for 3 daysand are then kept m w remaining on the agar surface are examined forgerminader normal glasshouse conditions for 15918 days. At tion. Theresults obtained in this test with a number of the end ofthis time threeleaves are removed from each the compounds of the invention are shown inTable II. plant and examined; thenurnber of, lesions per leaf is (3)Impregnalion t I thi t t agar plates are counted. The average number oflesions. per leaf in the prepared in which the agar contains thesubstance under treated plants is ei pressed as a percentage of; theavertestat a concentration of 10 parts per million the subge numb r flesions pet} leaf in e, untreated con r l; stance being introduced intothe hot agar from an acetone and 1 figure S gDM d pe ent ge solutionbefore the plate is poured. The centre of each plate isinoculated withBotrytis cinerea and the plates b c w i h ho i y m t abo spray areincubated; the size of the colony is measured nia-t t are u m e l t a rt t h mploy he, metrically at 3 day intervals and is compared withunatltlve Substance m the o m-o aflnaewsolg 8 9 treated controls. Theresults obtained in this test with five young tomato plants pl mafumlgatlon ama number of the compounds of the invention are shown f aVolume of 11 un 0-125 wot a 5% w./vi b IL solution of the substanceunder test in acetone is dis; (4) Damping-0;? fungi trials-In this testcubes of p rs d nto the chambe y m a s. O a Paint p y emit agarcontaining mycelium of either Pythium debaryanum T I aerosol lo 15 ll osfitfle 3 10 3 im Or Corticium solani are coated with dusts containing 53 Q 6 P S-f r m h f iga cham- 0:5% w./w. of the substance under test inkaolin and b ug a h 9 3 o z dq tq m f v m and placed in the centre ofagar plates. A measure of the, e m t assessed s c b d above h 1 73!activity of the compounds under test is obtained b 1 test. The resultsobtamed in the above tests are servation of the diameter of the coloniesat intervals, marised in Table I 7 Results obtained in this test with anumber of the com- (2) Groundsel mildewg-rln this test groups of 5ground-s Bwndg h invention are shown in Table II. sel plants growing inpotsinxa glasshouse are sprayed to Table II Damping 0t! Test Bunt ofImpregna- R1 3 2v Wheat tlon Test Pytlttum Corticium deban tmum aola'niMethyl. P C Ethyl C. 0. isoPropyln-But; Benzyl Phenyl isoButylp-Chlorophenyl n-Pentyl p-Tolyl m Chlorophenyln-Heptyl Phenyl P. MethyB.-- Ethyl... c, isoButyl Benzyl Phenyl Mo h l 1...- rylniliwr. ATetrahydropyridyl P .7 control (VG), good control (G), fair control (F).and poor control (P). 1

.(3) Apple mildew (Podosphaera leucotricha).'-This test is carried outin a similar manner to that described above for groundsel, mildewemploying apple seedlings growing in pots in a glasshouse. The resultsfare cx-, pressed in Table' III in like manner to'those obtained :theGroundsel mildew test.

,(4)' Applesc ab (Yenturia inaequalis).--The activity of a number of thecompounds of thefinvention has been assessed by small scale fieldtrials.Two trials have been carried out as follows: 7

I Site A: in this trial the trees were two year old Bramleys plantedclose together in a nursery and randomised blocks each containing fourtrees were used for each substance under test. The trees were sprayed torun off slit times between April and Iuly 1956, with aqueous suspensionscontaining 0.1% w./v. of active ingredient. An assessment of theeffectiveness of the compounds under test was made in the middle ofAugust by collecting'lOO leaves from each tree and measuring thepercentage area of each infected by the fungus. T heresults quoted inTable III are'averages of the percentage areas infected on the 400leaves collected from each block of trees.- For the purposesof'comparison control blocks of trees which received no treatment weresimilarly examined, the average degree of infection in the controlsbeing Site B: In this trial 8 -10 year old Lord Lambourne trees'wereused and each'substance under test was applied. to four trees. "Th e"trialiwas' carried out in ex-r actly the same manner as that conductedin Site A. The results obtained are summarised in Table HI. The averagedegree of infection on the leaves of control trees was 1.58%.

(5) Celery leaf spot.The activity of some of the compounds of theinvention against Septoria apii-graveolentis on celery plants wasdetermined in a similar manner to that described for the first of thetwo tomato leafmould tests. The results are summarised in Table III andexk,

pressed in the same manner as those obtained in the tomato leaf mouldtests.

I M.P. 136-141 C. 1(Found: C, 49.3; H, 5.3.

Ci H o N s rfequires c, 48.9; H, 5.2%. i

N n propyl p isothiocyanatobenzenesulphonan'iide.

layer is permanentl neutral. The chloro for'rn' ii Fis has: a meltingpoint of 96-97 C. 4.3. C H Q N S requires C, 44.6; H. 4.1%.)

1n exactly similar ;manner using the appropriate N substitutedsulphanilarnide, thereare prepared the fol lowing compounds.

N methyl p isothiocyanatobenzenesulphonamide. 137-139 C. (Found; C,42.3; H, 3.6; CgHgO gNzSg requires C, H, 3.5%.) V V N cyclohexylpisothiocyanatobenzenesulphonam H, 5.5.

ide. M.P. 141 -143- C. (Found: C, 52.9;

N ethyl- 'p isothiocyanatobenzenesulphonamide.'

M.P. 122-124 C. (Found: C, 45.0;

- H, 4.2. C H O N S requires C, 44.6; H, 4.1%.)

, N isopropyl p isothiocyanatobenzenesulphonamide.

M.P. 103-111" C. (Found: C, 46.6 H, 4.8. C H 'O N S requires C, 46.9; H,4.7%.)

M.P. 6870 'C. (Foundz' F C,' 49.3; C H lo NSg requires C, 48.9; H,5.2%.)

N n butyl 5 p isothiocyanatobenzenesulphonamide. M.P.'- 1199123? '0.(Foundz c, 48.8;

M.P. 119-l2l C. (Found: C, 46.9; H, 4.7. cmH gogNgsg requires H,

N benzyl p isothiocyanatobenzenesulphonamide. M.P. 123-131?" C.- (Found:a C, 55.0; H, 4.0. C H o N srequires 55.3; H, 4.0%.)

N phenyl p isothiocyanatobenzenesulphonamide.

121 124 "C. (Found: "C, 53.9; C H O N s requires C, 53.8; H, 3.5%.)

V N isobutyl p -'isothiocyanatobenzenesulphonamide.

The following ..non-limitative examples. illustrate the. invention. 7

EXAMPLE 1 QInthe preparation ofN:N-dimethyl-p-isothiocyanatobenzenesulphonamide a solution of 5:5 cc.of thiophosgene in cc. of chloroform is added to a suspension of 9.8grams of N :N -dimethylsulphanilamide in 25 cc.

Table III R1\ e N-SOQ-NOB R:

Tomato Leaf AppleScab Mould (percent Ground- -"Celery---- R R infection)sel Apple Leaf Spot- Mildew Mildew Percent 4 (percent infection Siteinfection) Spray Aerosol H n-Butyl--- 2o 44 P 0.11 B l i H n-PropyL- 542 G G 0.09. B 6.3 H n-PentyL. 4 12 G 1.25 B H p-Tolyl 1 F 0.69 A. 0

/N iii Plperldyl 4 .-14 VG G 0.73. A

C11H1402N2S2 requires C, 48.9; H,

N:N di n butyl 7 p isothiocyanatobenzenesulphom amide. M.P. 51.5-52.5 C.(Found: C, 54.9; H, 6.8. C H O N S requires C, 55.2; H, N (pchlorophenyl) p isothiocyanatobenzenesul-- phonamide. M.P. 1 23-126 C. I(Found: C, 48.0; H,-3.0f C H O N ClSi requires C, 48.1; H, 2.8%.) i

ofi N-hydrochloridacid-with stirring. i Potassium ear-5 phonamide; -MZP.134 -137 --C.1 (Found: 0,5 1.9; H, 6.8;;

bonate is added to the stirred mixture until the aqueous CmHggOgNgSgrequires C, H, 6.8%.)

NzN diethyl p isothiocyanatobenzenesulphonaniide.

N n hexyl p isothiocyanatobenzenesu-lphonam;.

ide. M.P. 114-115 C. (Found: C, 52.5; H, 6.1. C H O N S requires C,52.4; H, 6.0%.).

N n heptyl p isothiocyanatobenzenesulphoname ide. M.P. 110-112 C.(Found: C, 53.5; 'H, 6.6. C H O N S requires C, 53.8; H, 6.4%.) V i N--v (3 methylbutyl) p isothiocyanatobenzenesulphonarnide. M.P. 135-136:C. (Found: C, 50.6; H, 5.5. C H O N S requires C, 50.7; H, 5.6%.). v

N sec butyl p isothiocyanato-benzenesulphonamide. M.P. 100-102 C.(Found: C, 48.64;.H, 5.5., C11H1402N2S2 requires C,

p N (4 methylpentyl) p isothiocyanatobenzenesulphonamide. M.P. 92-94 C.(Found: C, 52.0, H, 6.1. C H' O N S requires c, 52.3, H, 6.0%.) p

N n dodecyl p isothiocyanatobenzenesulphonamide. M.P. 110 C. (Found: C,60.0; H, 80. C19H30O2N2S2 requires C, 59.7; H, H v

N" 'allyl p isothiocyanatobenzenesulphonarnide. M.P. 100-101 C. (Found:C, 47.5; H, 3.8. C10H1002N2S2 requires C, 7H,

N:N di n pentyl p isothiocyanatohenzenesulphonarnide. M.P. 35-37 C.(Found: C, 58.1; 1 1,7.4. Q H O N S requires C, 57.6; H, 7.35%.)

N o chlorophenyl p isothiocyanatobenzenesule. phonamide. M.P. 153-156.C. (Found: C, 47.8; H, 2.9. C H O N ClS requires C, 48.1; H, 2.8%.)

N m chlorophenyl p isothiocyanatobennenesul phonarnide. M.P. 115-117 C.(Found: C, 48.1; H, 2.8. C1 H O N ClS requires. C, 47.9; H, 2.8%.)

N p methoxyphenyl p isothiocyanatobenzenesul phonarnide. M.P. 125-126"C. (Found: C, 52..6;H,3.9. cuHizosNz z f q i fi i H. I

N o methoxyphenyl p isothiocyanatobenzenesule phonarnide. M.P. 119-121C. (Found: C, 52.2 ;1-1, 3,.9.

o gr o rus requires c, 52.5; 3.75%.

Y ;N p ethoxyphenyl p isothiocyanatobenzenesuh phonarnide. M.P. 135-137"C. (Found: C, 54.2; H, 4.1

cisHia s a z r qu r C: 5 1). v r

N m nitrophenyl' p isothiocyanatobenzenesul rial in 400 cc. of water.

sulphanilamide in the. fotm Q? a crystalline splidgwhiclu;

has a melting point of 1255-1285 C. (FoundFC, 52.5; H','7-1'. CmH'wO N SICQUiIQS C, H,

N :Nl-di-isobutylsulphanilamide which; is employed in the preparation ofN:N-di-isobutyl-p-isothiocyanatobenzenesulphonamide is prepared in thefollowing manner.

52 grams of di-isobutylamine are added to a suspension of 111 grams, ofmoist p-acetamidobenzenesulphonyl, chloride estimated to contain 42%w./w. of pure mate. The mixture so obtained is al lowed to stand, withoccasional shaking for 48 hours and; during this time it is kept neutralby the addition of w./v. potassium carbonate solution as required. After48 hours the solid produced is removed-by filtration and recrystallisedfrom ethyl acetate to give NzN-dieisobutyl-pacetamidobenzenesulphonamide in the form of a crystal v line solid whichhas a melting point of 137138 C.

(Found: C, 59.1; H, 8.0. C H O N S requires C, 58.9; H, 8.0%.) Thismaterialis hydrolysed in exactly simi-. lar manner to that describedabovefOr the hydrolysis of N -isobutyl-p-acetarnidobenzenesulphonamide.There is thus obtained N :N -di-isobutylsulphanilamide in, the

form of a crystalline solidwhich has a melting point oithiocyanatobenzenesulphonamide.

7.95. C H Q N' S requires C, 56.2; H, 7.8%.)

ph narn de- M.P. 137-13 (F0 n 6.465; 2.8..

C1a 9 4N3 2 qui 6-5; 2.7%.) e

N- methyl N phenyl -.p isothiocyanatobenzenfisul phonamide. M.P.112-117C. (Found: C, 55.7; 1 1,40.

N n p py e N phe yl n i o e y natob n enee sulphonamide. M.P. 128-129 C.(Found: C, 5,7.6; .1 I, 4.9., C H O N S requires C, 57.7; H, 4.8%.)

I N n butyl N phenyl -.p e isothiocyanatobenzene sulphonamide. M.P.97-98 C. (Found: C, 5,-9. 3; H, 5.4. C H O N S- requires C, 58.9; H,5.2%.)

N e ethyl N phenyl p, isothiocyanatobenzenesulu phonamide. M.P. 110 C.(Found: C, 56.85; H, 4.5. C15H14O2N2SZ requires C, 56.6; H, 4.4%.)

N-benzyl-N-methyl p isothiocyanatobenzenesulphonamide, M.P. 123-124 C.(Found: C, 56.3; H, 4.6 C H O N S requires C, 56.6 H, 4.4%.)

N ethyl-m-isothiocyanatobenzenesulphonamide, M.P., 77 C. (Found: C,44.8; 4.3 C H O N S requires C, 44.7; H, 4.1%.)

Nl-isobutylsulphanilamide which is employed'in the preparation ofN-isobutyl p isothiocyanatobenzenesul; phonamide is prepared in thefollowing manner. A mixture of 20 grams ofN-isobutyl-p-aefitflmidobenzenesulphonamide and 100 cc. of 6 Nhydrochloric acid is heated under reflux for 10 minutes. The clearsolution so ob tained is neutralised by the addition of sodium hydroxideolutio and e pre ip so p oduc d is rec y a lised. item. ethyl. acetate.Ihgre is thus. obtained, N-i$.ohutyl- 147-150 C. ,(Found: C, 59.3; H, 8.6. C H O N S, 4

,propylsulphanilamide in the form of a crystalline solid;

which has a melting point of 121-124 C. and which is, employed in thepreparation of N:N-di-n propyl-p-ism (Found: C, 56.4; H,

In exactly similar manner using the appropriate amine, there areobtained the followingcompounds which are employed as intermediates inthe preparation of com pounds described above. p

N -n-hexylsulphanilamide, M.P. 126-129 C. (Found: C, 55.9; H, 7.8. CQH ON S requires C, 56.25; H, 7.8%.) 4 l "N -n5heptylsulphani1amide, M.P.119-121 C. (Found: c,- 57.9;' H,'8.3.. c nons s requires c, 57.8; H,8.15%.)

N -(3-methylbutyl')sulphanilamide, M.P. -127 C (Found: C, 54.3; H, 7.4.C H O N S requires C, 54.5; H, 7.45%.)

N sec butylsulphanilamide, M.P. 132-135 G.

(Found: C, 52.2; H, 7.0. C H Q N S requiresC, 52.6;

N 4-m'ethylpentyl') sulphanilamide, M.P. '1401.42 C... (Found: C, 55.9;H,7=.8. C H O N S requires C, 56.25;, H, 7.8%.) Y r N :N-(di-n-pentyl)sulphanilamide, M.P. 55-58 C.

. N -(o-ehlorophenyl)sulphanilamide, M.P. 169-172" C. (Found: C, 50.7;H, 3.8. C H O N ClS requires C, 51.0; H, 3.9%.)

' -N -(m chlorophenyl)sulphanilamide, M.P. 132-135- C- (Found: C, H,4.0. C12H1102N2C1S requires C, 51.0; H, 3.9%.)

N -(o-methoxypheny1) sulphanilamide, M.P. 197-201 C. (Found: C, 55.75;H, 5.3. C H O N S requires C, 56.1; H, 5.0%.) f

N -pheny1-N -n-propylsulphanilamide, M.P. 105-107" C. (Found: C, H, C HO N SrequireS- 62,1; H, 6. 2%.)

N -n-butyl-N phenylsulphanilamide, M.P. 6870 C. (Found: C,- 62.9; H,6.5. C H O N S requires C, 63.2; H, 6.6%.) I

N ethyl N phenylsulphanilamide, M.P. C. (FOuIldI C, 60.5; H, 6.0.CmHmOzNgS requires C, H, 5.8%.) w

N -benzyl-N -methylsulphanilamide, M.P. 131-134 6. (Found: C, 60.7; H,5.8. C H O N S requires C, 60.9; H, 5.8%.) g

, EXAMPLE 2 Inthe preparation of N-n-pentyl-p-isothiocyanatobeueaccesses zenesulphonaniide, a solution of 3 cc. offthiophosge'n'ein" 2'0cc.-of chloroform is added to a suspension of 8 grams; of, N-n-pentylsulphanilamide in 16 cc. of 2 N hydrochloric acid withstirring. Potassium carbonate is added to the stirred mixture until theaqueous layer is permanently neutral. The chloroform layer is separated,dried over anhydrous'sodiurn sulphate and evaporated to dryness. Theresidue is recrystallised from petroleum ether (boiling range 100-120C.). There is thus obtainedN-n-pentyl-p-isothiocyanatobenzenesulphonamide in the form of acrystalline solid which has a melting point of 1;l31l5 C. (Found: C,50.9; H, 5.9. C H O N S requires C,'50.7; H, 5.6%.) V N -npentylsulphanilamide employed in the above preparation is prepared inthe followingmanner. 18 grams of, n-pentylamine are added to asuspension of 55 gramsof moist p-acetamidobenzenesulphonyl chlorideestimated to contain 42%;w./w. of pure-material in 200 cc. of water. iThe mixture so obtained is allowed to stand with occasional shakingfor48 hours and during this time it'is Kept neutral by the addition of20% w./v. potassium carbonate solution as required. After 48 hours thesolid produced is removed by filtration and recrystallised from ethylacetate togive N -n-pentyl-p-acetamidobenzenesulphonamide in the form ofa crystalline solid which has a melting point of 117-121 C. (Found: C,54.7; H,'7.2. CQH OQN S requires C, 54.9; H, 7.1%.) This material isheated under reflux for 10 minutes with 100 cc. 0156 N hydrochloricacidThe clear solution so obtained isneut'ralised by the'laddition ofsodiumhydroxide solution and the precipitate so producedisrecrystallised from alcohol. There is thus obtained N -npentylsulphanilamide inthe form Iota crystalline solidwhich has amelting point of 1214-127 0. (FoundziC, 54.6 7.2. c nmo n s requiresC,54:5;H', 7.45%.) 1 j" V 35 1 (a) In the preparation of.p-isothiocyanatob'enzenesulphonpiperidide a solution of 17 cc. ofthiophosg'ene in 100 cc.-of chloroforrnis added to a suspension of 48gram'sof sulphariilpiperidide in 100 cc. of 2 N hydro chloric acid withstirring. Sodium bicarbonate is. added to'the stirred mixtureuntil'theaqueous layer is permanently neutral. The chloroform-layer is separated,dried over anhydrous sodium sulphate and evaporated to dryness. Theresidue is recrystallised from -a-mixture of equal volumes oftrichloroethylene andpetroleum ether (boiling range 60-80 C.). There isthus obtained pisothiocyanatobenzenesulphonpiperidide in the, form of acolourless 'crystalline solidwhich has a melting point 5 of 125-128 C.(Found: C, 51.1; H, 4.9.

requires C, 51.1; e a

In exactly similar manner using sulphanilpyrrolidide 55 and.sulphanilmorpholide respectively in place 0f1sulphanilpiperidide, thereare prepared the following compounds: Vp-isoThiocyanatobenzenesulphonpyrrolidide, M.P..117- 118 C. (Found: 7C,479.4;7H, ,'C1IH12O2N2S2 [cf quires C, 49.3; H, 4.5%.) j 'cp-isoThiocyanatobenzenesulphonmorpholide, M.P., 113- 114 C. (Found: C,46.5, H,*4.3. C H O N S requires C, 46.5, H, 4.2%.) r r jp-isoThiocyanatobenzenesu M.P. 105107 C. (Found:.C, 52.45, H, 5.65,? a rp-isoThiocyanatobenzenesulp 8688 C. (Found: C, 52.9; H, 5.5.

I 1s 16 2 2 a requires C, 52.7; H, 5.4%.)

p-isoThiocyanatobenzenesulphon A tetrahydropyridide, M.P. 98-101 ,:C."(Foundz C,51.5; H-, 4.5. 7

lphon 3 methylpiperidide 6 hon 2 methylpiperidide, 7o

' m m z z a' requires C, 51.4;.H, 4.3%.) l

p-isoThiocyanatobenzenesulphon 4 methylpiperidide, M.P. l08111 C.(Found: C, 52.7; H, 5.7.

requires C, 52.7; H, 5.4%;) "Sulphanil-3-methylpiperidide which is usedas starting material in the preparation ofp-isothiocyanatobenzenemanner. 'A mixture of 59 grams ofp-acetamidobenzenesulphonyl chloride and 31 grams of 3-methylpiperidinein a small volumeof water. is shaken from time to" time and keptalkaline with sodium carbonate. After 4 days the solid which separatesis isolated and recrystallised from methanol to givep-acetamidobenzenesulphon-3- methylpiperidide methanolate, M.P. 78-82 C.(Foundi C, 54.8; H, 7.4. C H O N S requires C, 54.9; -H, 7.3%.) Thismaterial is hydrolysed by boiling for ten minutes with an excess of 6 Nhydrochloric acid. The clear solution so obtained is neutralised by theaddition of sodium hydroxide solution and the solid which separates isrecrystallised from methanol. There islthus obtainedsulphanil-3-methylpiperidide in the form'of a crystalline solid whichhas a melting point of 125'-130 C. (Found: C, 56.5; H, 7.3. C H O N- Srequires C,- 56.7; H,.7.1%.) In exactly similar [manner using2-rnethylpiperidine, 4-methylpiperid1ne and A -tetrahydropyridinerespectively in place of 3-methylpiperidine the following compounds areprepared. s i V v 'Sulphanil 2 methylp (Found; C, 56.45; H 56.7; H,7.1%,.)

= Sulphanil-4-methylpiperidide, 'M.P.' -112 C. (Found: C, 56.75; H, 7.0.c n go ms requires C, 56.7; a, 7.1%.) 7]

Sulphanil-n -tetrahydropyridide, M.P. 172 -l75 C. (Found: C, 55.2;H,.6.0. C H O N 'S requires C, 55.5; I V f.

' (b) In the preparation of p-isothiocyanatobenzenesulphonpiperidide62.5 :cc'. of redistilled trichloromethanesulphenyl chloride is slowly"added to a stirred mixture of grams of sulphanilpiperidide, 500 cc. ofalcohol free chloroform, 169 grams of stannous chloride, 525 cc. of 2 Nhydrochloric acid and'225 ccQOf'Water." The reaction mixture isstirredifor 2.5 hours, filtered through kieselguhr and separated into achloroform layer and an aqueous layer. The aqueous layer is extractedwith chloroform (2 X50 cc.) and these extracts are combined with themain chloroform layer. The combined solution is dried over anhydroussodium sulphate'and the chloroform, removed by distillation underreduced pressure. The residueis washed with cc. of petroleum ether(boiling'range 60-80 C.) and recrystallised from trichloroethylene.There is thus obtained p-isothiocyanatobenzenesulphonpiperidide in theform of a crystalline solid which is identical with the productdescribed in(a)above.' l

In exactly similar manner using N -methyl-N -phenylsulphanilamide inplace of sulphanilpiperidide there is obtained'N-methyLN-phenyl-p-isothiocyanatobenzenesulphonamide which is identicalwith the compound listed as prepared by the method described in Example1.

EXAMPLE 4 ',In the preparation of p-isothiocyanato-N-(p-tolyl)-benzenesulphonamide a solution of 33 cc. of thiophosgene in 300 cc..of.chloroform is added to a suspension of 93 grams of N-(p-tolyl)sulphanilamide in 360 cc. of N. hydrochloric acid withstirring. Sodium bicarbonate is. added to the stirred mixture untilgtheaqueous layer is permanently neutral. The chloroform layer is separated,dried'o'ver anhydrous' sodium sulphate and evapo- 5 rated to dryness.-The residue is recrystallised from iperidide, M.P. 109417 c.

s'ulphon-3- methylpiperidide is prepared in the following.

EXAMPLE 5 In the preparation of a dispersible. powden 20 parts by weightof N-n-butyl-p-isothiocyanatobenzenesulphonamide is intimately mixedwith 8 parts by weight of Belloid T.D. (a condensate of formaldehydeand. an allgyl aryl sulphonate)v and 72 parts. by weight of kaolin, r'llis composition may be added to. water-to form a-disperi9n suitable; forhorticultural use.

EXAMPLE 6' In the preparation of a fungicidal dust, 51 parts by weightof N-n-butyl-p-isothiocyanatobenzenesulphonamide is intimately mixedwithz95 parts'by weight of kaolin.

Compositions similar to those described in, Examples 5 and 6 may beprepared in whichtlie activeingredient specifically mentioned isreplaced by any of} the compounds listed in Examples 1', 2.3v 811 0.4. l.i

EXAMPLE 7 In the preparation of a composition suitable for dispersion asan aerosol suflicient N-ethyl-p-isothiocyanatoben- I zenesulphonamide isdissolved in a mixture of 5 parts by volume of arachis oil and 95 partsby volume of substantially anhydrous acetone to obtain a compositionwhich contains 5% w./v. of active ingredient.

This composition is readily dispersed as an aerosol by mechanical means,for example, by the use of a paint spray gun.

Similar compositions may be prepared in which the active ingredient isone of the following compounds.

N-n-butyl-p-isothiocyanatobenzenesulphonamide.

' N-n-propyl-p-isothiocyanatobenzenesulphonamideN-phenyl-p-isothiocyanatobenzenesulphonamideN-isobutyl-p-isothiocyanatobenzenesulphonamideN-n-pentyl-p-isothiocyanatobenzenesulphonamideN-p-ethoxyphenyl-p-isothiocyanatobenzenesulphonamideN-n-hexyl-p-isothiocyanatobenzenesulphonamideN:N-di-n-propyl-p-isothiocyanatobenzenesulphonamideN-methyl-N-phenyl-p-isothiocyanatobenzenesulphonamidep-isoThiocyanatobenzenesulphonpiperididep-isoThiocyanatobenzenesulphonpyrrolidide EXAMPLE 8 In the preparationof a composition suitable for dispersion as an aerosol, sufiicientN-isopropyl-p-isothiocyanatobenzenesulphonamide is dissolved insubstantially anhydrous acetone to obtain a solution which contains 5%w./v. of active ingredient.

This composition is readily dispersed as an aerosol by mechanical means,for example, by the use of a paint spray gun.

Compositions similar to that described in Example 8 may be prepared inwhich the active ingredient specifically mentioned is replaced by any ofthe compounds listed in Examples 1, 2, 3 and 4.

14 EXAMPLE 9 In the preparation of a dispersible powder 10'parts byweight of N-n-propyl-p-isothiocyanatobenzenesulphonamide is intimatelymixed with 8 parts. by weight of Belloid T.D. (a condensate formaldehydeand an alkyl aryl sulphonate)a and 82 parts byweight of kaolin. Thiscomposition may be addedtoI water to. form av dispersion suitable forhorticultural use.

In exactly similar manner compositions may be pre pared which containone of the following compounds as active ingredient.

N-r -butyl paisothiocyanatobenzenesulphonamide N -r 1 :pentyl-p;isoth it c;yanatobenzenesulphonamidev pisQ uqcxan tobenzenes pho p n i ideN-nhenybmimthiQ x na Qbenzen s lnhnnamide EXAMPLE 6 In the preparationof a dispersible powder 10. parts by weight ofN-p-tolyl-p-is0thiocyanatobenzenesulphonamide is intimately mixed with 8parts by weight of Belloid T.D. (a condensate. of formaldehyde and anvalkylaryl sulphonate), 5 parts by weight of Nansa S um. salt-0f nal yaryls lp u c acid) parts by weight of'kaolin. This composition may beadded to water to form ardispersion suitable for horticultural use.

Inexactly similar manner a composition may be pre- 1 pared whichcontains N-methyl N-phenyl-p-isothiqcyana tobenzenesulphonarnide as;active ingredient.

EXAMPLE 11 In the preparation of a composition which is suitable fordilution with water to produce a dispersion sufiicientN-ethyl-p-isothiocyanatobenzenesulphonamide is dissolved insubstantially.anhydrous acetone containing. 1.2%. v.'/v'. of EthylanC.P. (a polyethylene oxide condensate of octylphenol) to obtain acomposition which contains 40 10% w./v. of active ingredient.

In exactly similar manner compositions may be prepared which contain asactive ingredient one of the following compounds.

N-n-propyl-p-isothiocyanatobenzenesulphonamideN-n-butyl-p-isothiocyanatobenzenesulphonamideN-n-pentyl-p-isothiocyanatobenzenesulphonamideN-n-hexyl-p-isothiocyanatobenzenesulphonamideN-phenyl-p-isothiocyanatobenzenesulphonamideN:N-dimethyl-p-isothiocyanatobenzenesulphonamide 5oN:N-diethyl-p-isothiocyanatobenzenesulphonamideN:N-di-n-propyl-p-isothiocyanatobenzenesulphonamideN-methyl-N-phenyl-p-isothiocyanatobenzenesulphonamide EXAMPLE 12 In thepreparation of a composition which is suitable for dilution with waterto produce a stable emulsion suflicientN-methyl-N-phenyl-p-isothiocyanatobenzenesulphonamide is dissolved in amixture of 10 parts by volume of Ethylan SE. (a mixture of lauricdiethanolamide and a.

polyethylene voxide condensate of octylphenol) and 90 parts by volume ofbenzene to obtain a composition which contains 2 0% w./v. of activeingredient.

EXAMPLE 13 In the preparation of a composition which is suitable fordilution with water to obtain a stable emulsion sufiicient pisothiocyanatobenzenesulphonpiperidide is dissolved in a mixture of 10parts by volume of Ethylan SE. (a mixture of lauric diethanolamide and apolyethylene oxide condensate of octylphenol) and parts by volume ofbenzene to obtain a solution which contains 3 10% w./v. of activeingredient. r

A similar composition may be prepared using toluene (5 in place ofbenzene.

r m M w I men-me 15 We claim: n "1? organic isothiocyan'ate of theformula 1.Anorganicisothiocyanateoftheformule J j: y J News, N Q 2 NosTi Q l N S G which R and R eech representlower 51m; 1 t

m which Y 15 a mogen comammg radlcal 99? 6..pqsoThrocyanatobenzenesulphonprpendlde.1;

the group conslstmg of Z N and I r 7 I 7;: N methyl N phenyl pisothiocyanatobenzener r I in j sulphonamidei e g N- n 10 8; N-isopropYlp-isothiocyanatobenzenesu1phonamide.- "19.-N-n-butyl-peisothiocyanatobenzenesulphonamide;' wherein Z=N isselected from thegroup GOnsistin fi ig f p'ulsothlocyanatqben'zenq ofpiperidyl, lower alkylpiperidyl, pyrrolidyl and tetra: hydropyridyl R isselected from thegroup consisting of hydrogen and lower alkyl; and k isselected from the group consisting of lower alkyl, lower alkenylfphenyllower alkyl, phenyl, lower alkylphenyl, halogenated phenyl and loweralkoxyphenyl.

11. p isoThiocyanatoloenzenesulphon 4 methylpiperidide.

References ited injthe of thisn'pqt ent; w UNITED STATES PATENTS 2 2. Anorganic isothiocyanate'of the formula 2,042,600 QfI-lilg'er'et alr 1;June 2;193 6 i 2,339,050' 7 Carson Jan. 11, 1944 Y so 2,310,405 KaseFeb. 27,19 45 2,394,915 Jones Feb. 12,1946 l r 5 2,428,843 Georges Oct.14, 1947 1 2,517,760 Bosteta1, Aug. 8, 1950 3- An organlc lsothlocyanate 2 Newcomer J e 5 NCS i 2,735,101 Urbschat Marr12, 1951 N so,- H 12,785,190 Klopping Mar.-12, 1957 H R17 7 7 1 Q: H V e I F R PATENTS Iinwhich R is a hydrogen atom and R is lower aIkyI. 481,733 [GreatBritain 11 ,1938

4. An organic iso'thiocyanate o f 'the formula f517,6827 V 3, N03753,171 \N 'so, 210.833 7 V I]; as OTHE -RE E ENCES inwhich his loweralkyl and R is phenyl. I Q Q F f' 0 7 (19462

1. AN ORGANIC ISOTHIOCYANATE OF THE FORMULA
 11. P - ISOTHIOCYANATOBENZENESULPHON - 4 - METHYLPIPERIDIDE. 